Role of paraventricular angiotensin AT(1) receptors in salt-sensitive hypertension in mRen-2 transgenic rats

We have previously demonstrated that mRen-2 transgenic [Tg(+)] rats show a salt-induced exacerbation of hypertension (Callahan, M., P. Li, C. M. Ferrario, D. Ganten, and M. Morris. Hypertension Dallas 27: 573-577, 1996). In this study, we examined the role of paraventricular (PVN) angiotensin type-1 (AT(1)) receptors in the salt sensitivity of this model. Male Tg(+) and Tg(-) rats were instrumented with PVN cannulas for intracerebral drug administration and carotid catheters for chronic cardiovascular monitoring. Substitution of 2% NaCl for drinking water for 4 days caused a significant elevation (23 mmHg) of mean arterial pressure (MAP) in Tg(+) rats but not in Tg(-) rats. PVN injection of AT, receptor antisense oligodeoxynucleotides (ASODN), but not scrambled oligodeoxynucleotides (SCODN), produced a rapid decrease in MAP of 24 +/- 8 mmHg in salt-treated Tg(+) rats. There was no effect of either AT(1) ASODN or SCODN on MAP in salt-loaded Tg(-) rats or in Tg(+) rats consuming tap water. Salt loading significantly increased subfornical organ AT(1) receptors in Tg(+) rats with no changes produced by ASODN or SCODN. In contrast, there was a 40% decrease in PVN AT(1) receptors 20 h after direct PVN injection of AT(1) ASODN injection, compared with SCODN in Tg(+) rats. We conclude that PVN AT(1) receptors are critical in the expression of salt sensitivity in mRen-2 transgenic rats.